There is a need for developing an in vitro tumorigenesis model which mimics the in vivo biology of tumors. At present, tumor studies mostly utilize monolayer cell cultures and animal-derived biomatrix systems. The commonly used Matrigel and collagen models exhibit major compositional and biological limitations. Moreover, no well defined functional model is available for examining the important stages of tumor development in humans. DSI recently created a novel human biomatrix system, HuBiogel, for exploring cell-matrix interactions. Its physiologic matrix milieu, unlike existing models, actively supports proliferation, organization and differentiation of epithelial and endothelial cells. Employing this versatile biomatrix technology, DSI proposes to develop new physiologically-relevant (3D) models of human tumor invasion and angiogenesis. These tumor-host bioassay systems would allow analysis of discrete cellular and molecular events of tumor growth and progression in vitro. The Phase I specific goals are: 1. Develop and optimize HuBiogel assay systems using defined biomatrix formulations and 3D cell culture configurations and; 2. Demonstrate practical applications for monitoring key tumorigenesis events using multicellular tumor spheroid cocultures with fibroblasts or endothelial cells. In the second phase of this R&D project, functional studies of new bioassays will be expanded for validation with other human tumor models. The timely development of this clinically relevant model will positively impact cancer biology, drug discovery and therapeutic arenas. Commercial Importance & Significance: No acceptable commercial tumor model currently exists which utilizes a defined human biomatrix system. DSI will develop reusable and disposable 3D tumor invasion and angiogenesis bioassays. Sale of HuBiogel and pre-packed assay systems would have a significant world-wide market, both as a research and diagnostic tool.